Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with excessive industrial exposure to silicon and an elevated silicon content in his renal tissue was found to have a distinctive nephropathy, characterized pathologically by changes in the glomeruli and proximal tubules, and manifested clinically by albuminuria and hypertension. Proximal tubular function was intact. From a biochemical standpoint, this finding correlates with the demonstration in vitro that, in contrast to cadmium, a known cause of Fanconi syndrome, silicon does not inhibit renal cortical sodium-potassium-adenosine triphosphatase (Na-K-ATPase).
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PMID:Silicon nephropathy. 113 57

Hypertension is known to potentiate the risk of congestive heart failure (CHF) in diabetic individuals. Receptor-effector systems for atrial natriuretic peptide (ANP), which is known to regulate intracellular calcium (Ca2+), were studied in the kidney during hypertensive-diabetic cardiomyopathy in rats. Animals were divided into four groups: control, diabetic (D), hypertensive (H), and diabetic plus hypertensive (D + H). Diabetes was induced by a streptozotocin (65 mg/kg) injection and hypertension was induced by abdominal aortic constriction; studies were done at 1 and 6 weeks. Plasma ANP was increased at 1 week in the D, H, and D + H groups. There was a significant increase in the activity of Ca2+ + magnesium (Mg2+) adenosine triphosphatase (ATPase), which acts as a Ca2+ pump, in the kidney basolateral membrane from D, H, and D + H group at the 1 week study. Ca2+ + Mg2+ ATPase, on the other hand, was significantly decreased in the D + H group only at 6 weeks. This was associated with a decrease in plasma ANP, an increase in the kidney ANP receptor number, and a decrease in guanylate cyclase activity. The response of the Ca2+ pump to ANP was also attenuated. Since ANP is known to mediate its cellular effects in part by increasing Ca2+ + Mg2+ ATPase, the observed changes in the D + H group may contribute to the development of nephropathy and CHF.
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PMID:Congestive heart failure in diabetes with hypertension may be due to uncoupling of the atrial natriuretic peptide receptor-effector system in the kidney basolateral membrane. 164 1

The role of extrarenal potassium homeostasis is well recognized as a major mechanism for the acute defense against the development of hyperkalemia. The purpose of this report is to examine whether or not the various mechanisms of extrarenal potassium regulation are intact in patients with end-stage renal disease (ESRD). The available data suggest that with the development of ESRD and the uremic syndrome there is impaired extrarenal potassium metabolism that is related to a defect in the Na,K-adenosine triphosphatase (ATPase). The responsiveness of uremic patients to the various effector systems that regulate extrarenal potassium handling is discussed. Insulin is well positioned to play an important role in the regulation of plasma potassium concentration in patients with impaired renal function. The role of basal insulin may be even more important than previously appreciated, since somatostatin infusion causes a much greater increase in the fasting plasma potassium in rats with renal failure than in controls. Furthermore, stimulation of endogenous insulin by oral glucose results in a greater intracellular translocation of potassium in uremic rats than in controls. Under at least two common physiologic circumstances, feeding and vigorous exercise, endogenous catecholamines might also act to defend against acute increments in extracellular potassium concentration. However, it is important to appreciate that the response to beta 2-adrenoreceptor-mediated internal potassium disposal is heterogeneous as judged by the variable responses to epinephrine infusion. Based on the evidence presented in this report, a regimen for the treatment of life-threatening hyperkalemia is outlined. Interpretation of the available data demonstrate that bicarbonate should not be relied on as the sole initial treatment for severe hyperkalemia, since the magnitude of the effect of bicarbonate on potassium is variable and may be delayed. The initial treatment for life-threatening hyperkalemia should always include insulin plus glucose, as the hypokalemic response to insulin is both prompt and predictable. Combined treatment with beta 2-agonists and insulin is also effective and may help prevent insulin-induced hypoglycemia.
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PMID:Extrarenal potassium tolerance in chronic renal failure: implications for the treatment of acute hyperkalemia. 156 35

Aldose reductase is a rate limiting enzyme in the polyol pathway associated with the conversion of glucose to sorbitol. The enzyme is located in the eye (cornea, retina, lens), kidney, myelin sheath, and also in other tissues less involved in diabetic complications. Experiments in diabetic animals have implicated sorbitol accumulation in the lens to the development of cataracts. The use of inhibitors of aldose reductase in animal studies has demonstrated that diabetic complications such as cataracts, nephropathy, and slowing of nerve conduction can be ameliorated. While an osmotic effect can explain the physical changes in the lens leading to cataract formation, the effect of sorbitol accumulation in other tissues and the resulting diabetic complications has been linked to the depletion of myoinositol content resulting in a derangement of sodium-potassium adenosine triphosphatase activity. Since glucose and other hexoses are poor substrates for aldose reductase, it is only in hyperglycemia when the enzyme hexokinase is saturated that aldose reductase is activated, leading to accumulation of sorbitol. The kinetics of inhibition of aldose reductase by a variety of inhibitors has been delineated. The dose required varies from inhibitor to inhibitor and is consistent with their inhibition constants. Toxicity is a consideration in the use of some of the inhibitors, as was demonstrated with sorbinil which caused hypersensitivity reactions in 10 percent of patients. Other inhibitors such as tolerant have shown efficacy and are under clinical investigation. Interpretation of results obtained with aldose reductase inhibitor therapy in human subjects suggest that these inhibitors are effective at early stages of diabetic complications.
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PMID:Aldose reductase and its inhibition in the control of diabetic complications. 845 42

Lymphocytes from patients with end-stage renal disease (ESRD) exhibit elevated cytosolic calcium concentration ((Ca2+)i), but the mechanisms responsible for this elevated (Ca2+)i have not been entirely elucidated. In addition, lymphocyte proliferative responses to mitogenic stimuli are suppressed in patients with ESRD. The objectives of the study were as follows: (1) to measure calcium influx and efflux in lymphocytes from patients with ESRD; (2) to measure the effect of the calcium regulator parathyroid hormone (PTH) on lymphocyte (Ca2+)i; (3) to measure cytosolic calcium signal in patients' lymphocytes after mitogenic stimulation. The three study groups were as follows: healthy subjects (control), patients with chronic renal failure (CRF) before the beginning of regular dialysis treatment, and patients undergoing regular hemodialysis (HD) treatment. Peripheral blood lymphocytes were tested in vitro for (Ca2+)i, Ca2+ influx, and membrane calcium-adenosine triphosphatase (CaATPase) activity. Cytosolic Ca2+ signals were traced after stimulations by PTH and by phytohemagglutinin (PHA). Baseline (Ca2+)i was significantly elevated in both ESRD groups. Ca2+ influx was enhanced and CaATPase activity was reduced in both ESRD groups. PTH caused a (Ca2+)i increase in normal cells in a dose-dependent manner. PHA caused a (Ca2+)i elevation, with a Ca2+ signal in both groups of patients with ESRD that was significantly smaller than that in the control group. These findings suggest that the high (Ca2+)i found in lymphocytes from patients with ESRD is the result of enhanced Ca2+ influx concomitant with reduced Ca2+ extrusion, as reflected by reduced CaATPase activity. The patients' elevated serum PTH levels may have contributed to the high (Ca2+]i. The impaired cytosolic (Ca2+)i response to PHA may explain in part the suppressed lymphocyte proliferative response to PHA in patients with ESRD.
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PMID:Impaired lymphocyte calcium metabolism in end-stage renal disease: enhanced influx, decreased efflux, and reduced response to mitogen. 1021 71

The Na,K-adenosine triphosphatase (ATPase), or sodium pump, has been well studied for its role in the regulation of ion homeostasis in mammalian cells. Recent studies suggest that Na,K-ATPase might have multiple functions such as a role in the regulation of tight junction structure and function, induction of polarity, regulation of actin dynamics, control of cell movement, and cell signaling. These functions appear to be modulated by Na,K-ATPase enzyme activity as well as protein-protein interactions of the alpha and beta subunits. In this review we attempt to differentiate functions associated with enzyme activity and subunit interactions. In addition, the consequence of impaired Na,K-ATPase function or reduced subunit expression levels in kidney diseases such as cancer, tubulointerstitial fibrosis, and ischemic nephropathy are discussed.
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PMID:Multiple functions of Na,K-ATPase in epithelial cells. 1613 88

The motor protein nonmuscle myosin II (NMII) through its interaction with the actin cytoskeleton constitutes the machinery of cell crawling and has an important role in driving locomotion and infiltration of immune competent cells during inflammatory response and immune reaction. Blebbistatin is a highly selective inhibitor of NMII adenosine triphosphatase. This study examined the effect of NMII inhibition by blebbistatin on inflammation. In vitro, blebbistatin markedly induced actinomyosin complex disassembly in various cultured immunocytes, and functionally impaired their motile activity and invasive capacity as assessed by the Boyden chamber motility assay and the matrigel invasion assay. In vivo, in a rat model of acute inflammation induced by tumor necrosis factor, blebbistatin obliterated renal sequestration of circulating fluorescence-labeled macrophages in a dose-dependent fashion. Moreover, in rats with progressive obstructive nephropathy, blebbistatin treatment exhibited a remarkable renoprotective effect, as evidenced by normalized kidney weight, improved gross morphology, and diminished histologic injury in the tubulointerstitium. This beneficial effect was associated with significant amelioration of renal inflammation, consistent with a primary anti-inflammatory action by blebbistatin. In addition, in rats with established obstructive nephropathy, blebbistatin pretreated macrophages showed obliterated recruitment into the inflamed renal parenchyma, denoting that blebbistatin directly impedes inflammatory infiltration by immunocytes. Collectively, our findings suggest that inhibition of NMII has a potent and direct anti-inflammatory effect on the basis of impairment of the actinomyosin powered locomotive machinery, which is essential for migration and infiltration of immune competent cells.
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PMID:Inhibiting nonmuscle myosin II impedes inflammatory infiltration and ameliorates progressive renal disease. 2006 48

Because kidneys consume a large amount of oxygen and are relatively inefficient in oxygen uptake, they are susceptible to hypoxia, especially in patients with advanced chronic kidney disease accompanied by loss of peritubular capillaries. Accumulating evidence suggests that chronic tubulointerstitial hypoxia acts as a final common pathway leading to end-stage renal disease. Some biologically active uremic retention molecules, considered as uremic toxins, accumulate as the renal function declines, and at this moment, more than 90 bioactive uremic toxins have been identified. Uremic toxins per se have been proven to accelerate the progression of renal failure. However, the causal relationship between uremic toxin and tubulointerstitial hypoxia remains unclear. Our studies provided direct evidence that uremic toxin dysregulates oxygen metabolism in the kidney. Indoxyl sulfate (IS), a representative protein-bound uremic toxin, increased oxygen consumption in proximal renal tubules, decreased renal oxygenation, and consequently aggravated hypoxia in the remnant rat kidneys. The increase in tubular oxygen consumption by IS was dependent on sodium-potassium adenosine triphosphatase and oxidative stress. Our work also indicated a possible connection between IS and the desensitization of the oxygen-sensing mechanism in erythropoietin-producing cells, which may partly explain inadequate erythropoietin production in hypoxic kidneys of end-stage renal disease patients. Studies of uremic toxins will open a new avenue in development of novel therapeutic approaches of kidney disease.
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PMID:Dysregulated oxygen metabolism of the kidney by uremic toxins: review. 2220 Apr 19